Single-Cell Atlas for ACDMPV Sheds New Light on Lung Development
Research By: Minzhe Gao, PhD | Jeffrey Whitsett, MD
Post Date: September 15, 2023 | Publish Date: Sept. 15, 2023
Perinatal Institute: Neonatology and Pulmonary Biology | Top Scientific Achievement
Most infants born with alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) die within the first few hours or days of life. The rare condition is caused primarily by mutations in the FOXF1 gene locus.
Now, a comprehensive study of infant lung tissues led by Minzhe Guo, PhD, and Jeffrey Whitsett, MD, has identified 35 distinct cell types in ACDMPV, including major epithelial, endothelial, mesenchymal and immune cell types.
Using single-nucleus RNA sequencing and single-nucleus chromatin accessibility analysis, the team documented distinct, cell-autonomous roles for FOXF1 in endothelial cells, fibroblasts and pericyte progenitors. Overall, the team found a marked decrease in the numbers of lung endothelial cells that help with oxygen and carbon dioxide exchange, which helps explain the respiratory distress suffered by infants born with ACDMPV.
The findings identify FOXF1 and its role in lung endothelial cells as new targets for developing potential therapies for ACDMPV and other lung disorders causing pulmonary vascular dysfunction. But just as importantly, the study offers a deep look at the cell types involved in early lung formation and function, which could help improve outcomes in multiple lung diseases throughout the lifespan.
“This study provides a blueprint for using rare monogenetic diseases to identify the general design principles of the human lung that will potentially be useful to develop better therapies also for other diseases in which the lung fails. An impressive feat indeed,” states an accompanying editorial written by Jonas Schupp, MD, and Naftali Kaminski, MD, of the Yale School of Medicine.
Cincinnati Children’s co-authors included Kathryn Wikenheiser-Brokamp, MD, PhD, Joseph Kitzmiller, Cheng Jiang, Guolun Wang, Yifei Miao, William Zacharias, MD, PhD, Yan Xu, Mingxia Xu, and Vladimir Kalinichenko. Experts with seven other institutions contributed. This study also was supported by the Pathology Research Core and the Single Cell Genomics Core.
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| Original title: | Single Cell Multiomics Identifies Cells and Genetic Networks Underlying Alveolar Capillary Dysplasia |
| Published in: | American Journal of Respiratory & Critical Care Medicine |
| Publish date: | Sept. 15, 2023 |
Research By
My research interests include developing novel computational methods and software tools to support single cell multi-omics data analysis and integration for scientific discovery or to facilitate data management, access, and visualization.
Jeffrey Whitsett’s laboratory makes extensive use of conditional gene targeting in transgenic mice, bioinformatics, physiology and biochemistry in the study of lung formation and function.
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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